1. Field of the Invention
This invention concerns benzoxathiole pyrrolidine compounds which affect the cardiovascular system and which are particularly effective as hypotensive agents. The invention is directed toward orally active, long lasting cardiovascular regulators of hypertension.
2. Related Disclosures
Compounds which most closely resemble, in molecular structure, the compounds of the present invention are useful in treating general disorders related to the cardiovascular system and other therapeutic applications.
Practolol and prenalterol which are amino-alcohol aryl ethers are well known and commercially available compounds which affect the .beta..sub.1 adrenergic receptors of the peripheral system. J. Med. Chem., 16:168 (1973).
In addition, there have been several deliberate attempts to combine .beta..sub.1 affectors with vasodilators such as, for example, compounds which are naphthalenone phthalazinylhydrazones, and which may be hydrolyzed in the body to form hydralazine, a well known peripheral vasodilator, and bunolol, a general .beta. adrenergic blocker (see U.S. Pat. No. 4,061,636). In addition, sulfinalol (British Pat. No. 1,544,872) and its relatives are known antihypertensive/antiarrhythmic agents.
Cyclic compounds containing a 5 or 6 membered saturated nitrogen-containing ring, linked through a hydroxymethyl group to an aromatic nucleus, such as, for example, rimiterol (Pinder, R. M. et al, Drugs, 14:81 (1977)) and other compounds disclosed in European Pat. No. 10460, Belgium Pat. No. 884176 and U.S. Pat. No. 4,342,692 have known physiological activities and are psychotropic, cardiotonic, antihypertensive, antiallergic, and hypolipaemic agents. Rimiterol, itself, is a known .beta..sub.2 agonist. Some of these hypotensive compounds have recently been described in European Pat. No. 22408.
British Pat. No. 1,392,674 also discloses, as agents for treatment of acutely depressed cardiac contractility, compounds related in structure to those of the invention herein.